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tay sachs

3K views 2 replies 2 participants last post by  islandcrazy 
#1 ·
A girl born to parents of eastern Mediterranean Jewish descent is brought to the pediatric neurology clinic. She appeared normal at birth and is now 6 months of age. There is a loss of peripheral vision and an abnormal startle response to auditory stimuli. She has suddenly shown a loss of coordination and has lost some responsiveness to her environment. She has a cherry-red spot on her macula. Treatments to cure this disease might focus on developing therapies that would do which one of the following?
A.
Stimulate ganglioside GM2 production

B.
Stimulate synthesis of GM2 by the rough endoplasmic reticulum (RER)

C.
Stimulate hexosaminidase production

D.
Stimulate transport of ganglioside GM2 to the lysosome

E.
Remove mannose 6-phosphate from hexosaminidase
 
#2 ·
child in the scenario suffers from Tay-Sachs disease, a lysosomal storage disease. Lysosomes contain an array of specific hydrolases. In Tay-Sachs disease, hexosaminidase A is deficient, resulting in the buildup of GM2 ganglioside in lysosomes leading to mental retardation, blindness, and mortality. A pharmacological approach would target reducing GM2 ganglioside levels by increasing hexosaminidase A activity (answer c). Increase in GM2 levels (answers a and b) or increased transport (answer d) to a lysosome deficient in hexosaminidase would worsen the disease. The table on the next page summarizes the enzyme deficiencies and resulting effects in some of the more prominent lysosomal disorders. Mannose 6-phosphate and its receptor are involved in the trafficking of proteins to the lysosomal compartment. Removal of mannose 6-phosphate (answer e), as occurs in inclusion-cell (I-cell) disease, would result in default of lysosomal enzymes to the secretory pathway, and the hexosaminidase deficiency would worsen.
 
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